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Introduction: External ventricular drains (EVDs) are crucial for treating neurocritically ill patients but are complicated by feared EVD-associated infections (EVDIs) in up to 35% of all inserted drains, contributing significantly to morbidity, mortality and account for a significant proportion of intensive care unit (ICU) antibiotic use. However, the lack of a universal definition for EVDIs leads to inconsistent diagnostic criteria across studies, with a concern of substantial overtreatment with broad-spectrum antibiotics. This study aimed to evaluate if current EVDI surveillance parameters can be optimized to better distinguish true from suspected EVDI.

Methods: We conducted a retrospective cohort study at the Karolinska University Hospital ICU, including all patients treated with EVDs between 2006 and 2023, excluding patients with primary central nervous system (CNS) infections. EVDI surveillance included biweekly sampling and cultures from cerebrospinal fluid (CSF). Patients were categorized as no infection (NI), suspected infection (SI), or verified infection (VI) based on culture results and treatment status. We employed classification and regression analyses to identify predictors of VI.

Results: Among 1,828 patients with EVDs, 29.8% were initiated on antibiotic treatment due to suspected infection and 4.1% were found to have culture confirmed infections. The main finding is that current accepted diagnostic parameters cannot distinguish aseptic inflammation from true EVDI. In multivariable logistic analysis the best models exhibited low accuracy, with a pseudo-R2 of only 0.06. CSF lactate was the most important metric in a univariable setting, however with a cut-off of 8.9 mmol/L it showed low discrimintive ability and limited clinical utility.

Conclusions: In this study we evaluate current accepted EVDI surveillance methods in, to our knowledge, the largest cohort of paired samples to date. We find that current surveillance parameters cannot distinguish aseptic CNS inflammation from true EVDIs in an ICU setting. This contributes to a significant antibiotic overtreatment, with 25% of our entire cohort being unnecessarily initiated on broad-spectrum antibiotics, a number we expect can be generalized. We identify a large clinical problem with consequences on both a individual and population level, and recommend that future research focus on evaluating new techniques, such as fast bedside sequencing methods.

Background: Knowing the individual child’s risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors.

Methods: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure.

Results: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores’ results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson–Todd Scale (AUC = 0.79) was all associated with death.

Conclusions: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.

Telomere length maintenance, in the vast majority of cases executed by telomerase, is a prerequisite for long-term proliferation. Most malignant tumours, including lymphomas, are telomerase-positive and this activity is a potential target for future therapeutic interventions since inhibition of telomerase has been shown to result in telomere shortening and cell death in vitro. One prerequisite for the suitability of anti-telomerase drugs in treating cancer is that tumours exhibit shortened telomeres compared to telomerase-positive stem cells. A scenario is envisioned where the tumour burden is reduced using conventional therapy whereafter remaining tumour cells are treated with telomerase inhibitors. In evaluating the realism of such an approach it is essential to know the effects on telomere status by traditional therapeutic regimens. We have studied the telomere lengths in 47 diagnostic lymphomas and a significant telomere shortening was observed compared to benign lymphoid tissues. In addition, telomere length and telomerase activity were studied in consecutive samples from patients with relapsing non-Hodgkin's lymphomas. Shortened, unchanged and elongated telomere lengths were observed in the relapse samples. The telomere length alterations found in the relapsing lymphomas appeared to be independent of telomerase and rather represented clonal selection random at the telomere length level. These data indicate that anti-telomerase therapy would be suitable in only a fraction of malignant lymphomas.